This study had two objectives: first, to determine the degree to which experiences of victimization by peers during adolescence led to a subsequent rise in depressive symptoms, and second, to identify genetic markers that predict depressive reactivity to victimization. We used a cohort sequential design to obtain a longitudinal sample of 1,475 adolescents (3,263 observations) in Grades 8 to 12 (56% female; 47% Black, 46% White). Multilevel growth curve models were used to assess whether victimization predicted depressive symptoms 6 months later, beyond baseline trajectories for depressive symptoms. We modeled the interactive effects of peer victimization with three genetic polymorphisms (on 5-HTTLPR, DRD2 TaqIA, and BDNF Val66Met) on depressive symptoms. Although victimization predicted subsequent depressive symptoms, there was substantial heterogeneity in the magnitude of the effect of victimization. Val alleles, associated with higher brain-derived neurotrophic factor (BDNF) functioning, predicted more sensitivity to victimization. Neither DRD2 TaqIA, a marker associated with dopaminergic functioning, nor 5-HTTLPR, a marker associated with serotonin activity, was associated with sensitivity to victimization. The social stress of peer victimization triggers depressive symptoms most strongly in individuals who are homozygous for the Val allele on the BDNF Val/Met polymorphism. This polymorphism has been linked with sensitivity to social defeat in animal models. Future research should explore behavioral, cognitive, and emotional explanations of the effects of BDNF Val/Met on responsivity to victimization.